title: Myeloid-derived suppressor cells play crucial roles in the regulation of mouse collagen-induced arthritis.
abstract: Myeloid-derived suppressor cells (MDSCs) are of myeloid origin and are able to suppress T cell responses. The role of MDSCs in autoimmune diseases remains controversial, and little is known about the function of MDSCs in autoimmune arthritis. In this study, we clarify that MDSCs play crucial roles in the regulation of proinflammatory immune response in a collagen-induced arthritis (CIA) mouse model. MDSCs accumulated in the spleens of mice with CIA when arthritis severity peaked. These MDSCs inhibited the proliferation of CD4(+) T cells and their differentiation into Th17 cells in vitro. Moreover, MDSCs inhibited the production of IFN-γ, IL-2, TNF-α, and IL-6 by CD4(+) T cells in vitro, whereas they promoted the production of IL-10. Adoptive transfer of MDSCs reduced the severity of CIA in vivo, which was accompanied by a decrease in the number of CD4(+) T cells and Th17 cells in the draining lymph nodes. However, depletion of MDSCs abrogated the spontaneous improvement of CIA. In conclusion, MDSCs in CIA suppress the progression of CIA by inhibiting the proinflammatory immune response of CD4(+) T cells. These observations suggest that MDSCs play crucial roles in the regulation of autoimmune arthritis, which could be exploited in new cell-based therapies for human rheumatoid arthritis.
authors.affiliation: Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Fujii
authors.forename: Eishi
authors.initials: E
authors.lastname: Ashihara
authors.forename: Hideyo
authors.initials: H
authors.lastname: Hirai
authors.forename: Hidetake
authors.initials: H
authors.lastname: Nagahara
authors.forename: Naoko
authors.initials: N
authors.lastname: Kajitani
authors.forename: Kazuki
authors.initials: K
authors.lastname: Fujioka
authors.forename: Ken
authors.initials: K
authors.lastname: Murakami
authors.forename: Takahiro
authors.initials: T
authors.lastname: Seno
authors.forename: Aihiro
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Ishino
authors.forename: Masataka
authors.initials: M
authors.lastname: Kohno
authors.forename: Taira
authors.initials: T
authors.lastname: Maekawa
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kawahito
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000628:therapy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D003094:Collagen; D007249:Inflammation / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D003094:Collagen